Association between statin use and ischemic stroke or major hemorrhage in patients taking dabigatran for atrial fibrillation
Bibliographic record
Abstract
BACKGROUND: Dabigatran etexilate is a prodrug whose absorption is opposed by intestinal P-glycoprotein and which is converted by carboxylesterase to its active form, dabigatran. Unlike other statins, simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase, and might either increase the risk of hemorrhage with dabigatran etexilate or decrease its effectiveness. METHODS: We conducted 2 population-based, nested case-control studies involving Ontario residents 66 years of age and older who started dabigatran etexilate between May 1, 2012, and Mar. 31, 2014. In the first study, cases were patients with ischemic stroke; in the second, cases were patients with major hemorrhage. Each case was matched with up to 4 controls by age and sex. All cases and controls received a single statin in the 60 days preceding the index date. We determined the association between each outcome and the use of simvastatin or lovastatin, relative to other statins. RESULTS: Among 45 991 patients taking dabigatran etexilate, we identified 397 cases with ischemic stroke and 1117 cases with major hemorrhage. After multivariable adjustment, use of simvastatin or lovastatin was not associated with an increased risk of stroke (adjusted odds ratio [OR] 1.33, 95% confidence interval [CI] 0.88 to 2.01). In contrast, use of simvastatin and lovastatin were associated with a higher risk of major hemorrhage (adjusted OR 1.46, 95% CI 1.17 to 1.82). INTERPRETATION: In patients receiving dabigatran etexilate, simvastatin and lovastatin were associated with a higher risk of major hemorrhage relative to other statins. Preferential use of the other statins should be considered in these patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".